Ca2+-sensitive inhibition by Pb2+ of α7-containing nicotinic acetylcholine receptors in hippocampal neurons

A. Mike, Edna F R Pereira, Edson X. Albuquerque

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In the present study the patch-clamp technique was applied to cultured hippocampal neurons to determine the kinetics as well as the agonist concentration- and Ca2+-dependence of Pb2+-induced inhibition of α7 nicotinic receptors (nAChRs). Evidence is provided that more than two-thirds of the inhibition by Pb2+ (3-30 μM) of α7 nAChR-mediated whole-cell currents (referred to as type IA currents) develops rapidly and is fully reversible upon washing. The estimated values for τ(onset) and τ(recovery) were 165 and 240 ms, respectively. The magnitude of the effect of Pb2+ was the same regardless of whether acetylcholine or choline was the agonist. Pre-exposure of the neurons for 800 ms to Pb2+ (30 μM) decreased the amplitude and accelerated the decay phase of currents evoked by moderate to high agonist concentrations. In contrast, only the amplitude of currents evoked by low agonist concentrations was reduced when the neurons were exposed simultaneously to Pb2+ and the agonists. Taken together with the findings that Pb2+ reduces the frequency of opening and the mean open time of α7 nAChR channels, these data suggest that Pb2+ accelerates the rate of receptor desensitization. An additional reduction of type IA current amplitudes occurred after 2-min exposure of the neurons to Pb2+. This effect was not reversible upon washing of the neurons and was most likely due to an intracellular action of Pb2+. Pb2+-induced inhibition of α7 nAChRs, which was hindered by the enhancement of extracellular Ca2+ concentrations, may contribute to the neurotoxicity of the heavy metal. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)112-123
Number of pages12
JournalBrain Research
Volume873
Issue number1
DOIs
Publication statusPublished - Aug 4 2000

Fingerprint

Nicotinic Receptors
Neurons
Patch-Clamp Techniques
Heavy Metals
Choline
Acetylcholine

Keywords

  • Acetylcholine
  • Choline
  • Electrophysiology
  • Hippocampus
  • Lead
  • Nicotinic receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ca2+-sensitive inhibition by Pb2+ of α7-containing nicotinic acetylcholine receptors in hippocampal neurons. / Mike, A.; Pereira, Edna F R; Albuquerque, Edson X.

In: Brain Research, Vol. 873, No. 1, 04.08.2000, p. 112-123.

Research output: Contribution to journalArticle

Mike, A. ; Pereira, Edna F R ; Albuquerque, Edson X. / Ca2+-sensitive inhibition by Pb2+ of α7-containing nicotinic acetylcholine receptors in hippocampal neurons. In: Brain Research. 2000 ; Vol. 873, No. 1. pp. 112-123.
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